Over the past decade, the ability to forecast weather and climate conditions on subseasonal to seasonal (S2S) timescales, i.e., two to fifty-two weeks in advance, has improved substantially. Although significant progress has been made, much work remains to make S2S predictions skillful enough, as well as optimally tailored and communicated, to enable widespread use. Next Generation Earth System Predictions presents a ten-year U.S. research agenda that increases the nation's S2S research and modeling capability, advances S2S forecasting, and aids in decision making at medium and extended lead times.